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Biomedical subjects

M Walker

Publications and source records attributed to M Walker.

At least 451 records · Page 25Linked to original sources

Increased indices of lipid peroxidation in stress-susceptible pigs and effects of vitamin E.

When stress-susceptible and stress-resistant pigs consumed diets containing 10 iu vitamin E kg-1, the stress-susceptible pigs had damaged cell membranes. This was indicated by increased plasma activities of creatine kinase and pyruvate kinase. Plasma concentrations of thiobarbituric acid reactive substances and conjugated dienes were also increased suggesting that the membrane damage was caused by free radicals. Susceptibility to free radicals was further demonstrated by an increased tendency for erythrocytes and tissue homogenates from stress-susceptible pigs to peroxidise when incubated with hydrogen peroxide and iron, respectively. Supplementation of the diets with approximately 20 times normal requirements of vitamin E decreased plasma creatine kinase and pyruvate kinase activities, and inhibited the formation of the indices of peroxidation in vivo and in vitro. It is concluded that the stress-susceptible pig has an abnormality in its antioxidant defence mechanisms. However, this abnormality was not due to a deficiency in selenium-dependent glutathione peroxidase, since activities were significantly increased in the longissimus dorsi of stress-susceptible pigs. Although the nature of the antioxidant defect is unclear, it is suggested that stress-susceptible pigs are under a sustained oxidant stress and that a decreased ability to accommodate even a normal free radical load may contribute to the rapid development of the fatal stress response.

Animals↗

Hepatitis.

Explore the source record for details and available documents.

Cross Infection↗

Alcohol and mortality in British men: explaining the U-shaped curve.

In a prospective study of 7735 middle-aged 7 British men, 504 of whom died in a follow-up period of 7.5 years, there was a U-shaped relationship between alcohol intake and total mortality and an inverse relationship with cardiovascular mortality, even after adjustment for age, cigarette smoking, and social class. These mortality patterns were seen in all smoking categories (with ex-smoking non-drinkers having the highest mortality) and were observed in manual but not in non-manual workers. The alcohol-mortality relationships (total and cardiovascular) were present only in men with cardiovascular or cardiovascular-related doctor-diagnosed illnesses at initial examination. The data suggest that the observed alcohol-mortality relationships are produced by pre-existing disease and by the movement of men with such disease into non-drinking or occasional-drinking categories. The concept of a "protective" effect of drinking on mortality, ignoring the dynamic relationship between ill-health and drinking behaviour, is likely to be ill founded.

Alcohol Drinking↗

Blood pressure in British children: associations with adult blood pressure and cardiovascular mortality.

Blood pressure was measured in 4186 children aged 5 to 7 years in 9 British towns. 3 towns had high, 3 had intermediate, and 3 had low adult blood pressure levels observed in an earlier study of middle-aged men. Significant differences between the towns were found for the children's mean systolic blood pressure (range 96.7 to 102.4 mm Hg) and diastolic pressure (range 55.9 to 60.3 mm Hg). The pattern of systolic blood pressure differences in children was similar to that observed in the study of middle-aged men (r = 0.65). The town mean systolic pressures in children show an association with standardised mortality ratios for cardiovascular disease in adults. The pattern of geographical differences in blood pressure observed in British adult men may have its origins early in life.

Adolescent↗

Visualization of domains in native and nucleotide-trapped myosin heads by negative staining.

Electron microscopy of negatively stained vertebrate skeletal muscle myosin molecules has revealed substructure suggestive of globular domains in the head portions of the molecule. This head substructure has been examined after both low and high electron doe. The results suggest it is probably not an artefact of radiation damage. The most common appearance is of one or two stain-filled clefts which run roughly perpendicular to the long axis of the head, giving rise to the appearance of two or three domains in a line. A large domain is located at the end of the head, while two smaller domains are arranged between this and the head-tail junction. The size of the large distal domain (about 10 nm long and about 7 nm wide at its widest point) is similar in heads showing either two or three domains. Stable analogues of M.ATP and M.ADP.Pi, the predominant complexes present during hydrolysis of ATP by myosin, were prepared by crosslinking the two reactive SH groups (SH1 and SH2) in the myosin head heavy chain with N,N'-p-phenylenedimaleimide (pPDM) in the presence of ADP, and by forming a complex with vanadate ion and ADP. At this resolution (approximately 2 nm) the heads of these modified molecules did not appear markedly different from those of the untreated protein, although there was a small increase in the number of straight as opposed to curved heads after cross-linking with pPDM.

Animals↗

Function of hormonally-induced corpora lutea in the domestic cat.

Hysterectomy (3 animals) or diversion of the uterine venous blood from the ovarian vasculature (3 animals) has no effect on the duration of hormonally-induced luteal activity in the pseudopregnant luteal-phase cat (control: 4 animals), suggesting that the uterus exerts no local or systemic influence on the duration of luteal function.

Journal Article↗

Effect of healing on compliance of porous Dacron grafts.

The effects of tissue ingrowth on the compliance of porous Dacron grafts were studied in 8 mm external-velour warp-knit Dacron grafts implanted in the canine descending thoracic aorta. The compliance of these grafts was measured before implantation and after implant periods of two weeks and one, two, four, and six months. Compliance, which initially was 0.043 +/- 0.008% mm Hg, decreased less than 10% after implantation (no statistical difference at p less than 0.05). No anastomotic neointimal hyperplasia was observed. Although the total thickness of the graft wall increased two- to three-fold after implantation, the benign healing process observed in this study had very little influence on graft compliance followed to six months.

Animals↗

Prediction of men at high risk of heart attack and its relevance to pilots.

In this paper we have extrapolated from data on the general population of middle-aged men and made suggestions for risk prediction and prevention policy in aircrew. As suggested previously, it would be helpful in future if data on the risk of heart attack in pilots could be generated from a central recording system covering both current pilots and those who retire for whatever reason. Indefinite follow-up information on ischaemic events would also be particularly helpful.

Adult↗

Parental death from heart disease and the risk of heart attack.

In the British Regional Heart Study, 7735 men aged 40-59 years were asked at initial screening whether their father or mother was alive or dead and to what cause any death had been attributed. They were followed up for the occurrence of major ischaemic heart disease events. At screening the men reported that 23% of the fathers and 43% of the mothers were alive and that 19% of the fathers and 11% of the mothers had died of heart trouble. In a sample of parental deaths, the death certificate was obtained and it was found that a son's report of a parental death from 'heart trouble' was a reliable indication that death had been certified to ischaemic heart disease. However, about half of the parental deaths certified as ischaemic heart disease were not reported as 'heart trouble' by their sons. A major ischaemic heart disease event was experienced by 336 men over an average follow-up of 6.2 years. Men who said their father had died from 'heart trouble' were at twice the risk of a major ischaemic heart disease event compared with men whose fathers were still alive and 1.5 times the risk of men who reported their father to be dead from another or unknown cause, even after accounting for age, systolic blood pressure, serum total cholesterol, cigarette smoking and serum HDL-cholesterol. For men with mother dead from heart trouble, the corresponding figures were 1.3 and 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pharmacological manipulation of adynamic ileus: controlled randomized double-blind study of ceruletide on intestinal motor activity after elective abdominal surgery.

In a double-blind placebo-controlled trial of patients undergoing elective abdominal surgery (n = 91), a single intravenous infusion of ceruletide (2.5 ng kg-1 min-1 for 1 hour) resulted in audible bowel sounds in 42/47 patients as opposed to 30/44 receiving placebo (P less than 0.025). Excessive bowel sounds were noted in 16 patients in the ceruletide group and four receiving placebo (P less than 0.01). Significantly more patients (P less than 0.01) in the ceruletide group (22/45 versus 9/44) passed flatus per rectum between the second and third post-operative day. Ceruletide infusion was accompanied by a significant increase in the incidence of nausea and vomiting (P less than 0.005, P less than 0.0025) but these side effects were short-lived. These results indicate that ceruletide is likely to be a useful therapeutic agent for acute intestinal adynamic motility disorders.

Abdomen↗

Non-ionic surfactant effects on hairless mouse skin permeability characteristics.

The influence of a range of polyethoxylated non-ionic surfactants upon the transport of methyl nicotinate across hairless mouse skin in-vitro was investigated using standard two-compartment diffusion cells. Those surfactants having a linear alkyl chain greater than C8 and an ethylene oxide chain length of less than E14 caused significant increases in the flux of methyl nicotinate. Surfactants having branched or aromatic moieties in the hydrophobic portion were ineffective. Maximum enhancement of flux was obtained using polyoxyethylene (10) lauryl ether (Brij 36T). Two possible modes of surfactant action are proposed. Initially the surfactant may penetrate into the intercellular regions of the stratum corneum, increase fluidity and eventually solubilise and extract lipid components. Secondly, penetration of the surfactant into the intracellular matrix followed by interaction and binding with the keratin filaments may result in a disruption of order within the corneocyte. The structural specificity required for the latter mechanism may explain, to some extent, the maximum activity obtained with the C12 surfactant.

Animals↗

The role of risk factors in heart attacks occurring in men with pre-existing ischaemic heart disease.

The importance of three risk factors--serum total cholesterol, systolic blood pressure, and cigarette smoking--on the risk of new major ischaemic heart disease events in men who already have evidence of ischaemic heart disease was assessed. Data from the initial examination in a large prospective study of cardiovascular disease in middle aged men (the British Regional Heart Study) were used to separate 7710 men into three groups on the basis of a resting electrocardiogram, a standardised chest pain questionnaire, and recall of a doctor's diagnosis of angina or of a previous heart attack: (group 1) no evidence of ischaemic heart disease (75%), (group 2) evidence of ischaemic heart disease short of a definite myocardial infarction (20%), (group 3) definite myocardial infarction (6%). In the average follow up period of 7.5 years, 443 men suffered a new major event caused by ischaemic heart disease (fatal or non-fatal myocardial infarction or sudden cardiac death). Age standardised event rates were determined for each of the three groups for varying levels of the established risk factors. Cigarette smoking is strongly associated with the event rate in group 1 but in men with existing heart disease, especially group 3, differences in risk between the smoking categories were smaller. The strong relation between systolic blood pressure and event rate persisted in groups 1 and 2 but not in group 3. The positive association between serum concentration of total cholesterol and the event rate was strongest in group 1 and weaker in groups 2 and 3, though it remained highly significant. These observations, taken together with the results of previous prospective studies and intervention trials, suggest that the important association between serum total cholesterol and the risk of heart attack persists in men with pre-existing ischaemic heart disease, including myocardial infarction. Therefore, in these men the reduction of serum total cholesterol concentration may be at least as important as it is in men without evidence of ischaemic heart disease.

Adult↗

Height and social class in middle-aged British men.

A study of 7735 middle-aged British men drawn from general practices in twenty-four towns shows that there has been a progressive increase in mean height in the men who were born between 1919 and 1939. This is true for both manual and non-manual classes, but the mean heights of the two groups are significantly different and remain widely separated over this period of time. Manual workers lag twenty years behind non-manual workers in their attained height. Data from other studies indicate that this social class difference in adult height is still present in those born up to 1960. The variation in mean height between the twenty-four towns is less marked than the variation in mean height between the social classes. After social class and age have been taken into account, a "town effect" on height is still present. If height is accepted as an indicator of socio-economic circumstances in childhood, then there is a difference in adult height between social class groups in Great Britain which does not appear to be diminishing.

Body Height↗

cis and trans control of erythroid cell-specific gene expression during erythropoiesis.

The overall aim of our group's work is to investigate the molecular mechanisms regulating erythroid cell-specific gene expression during erythroid cell differentiation. We have been successful in cloning two non-globin genes of interest: the first encodes the rabbit red cell-specific lipoxygenase (LOX), which has a role in degrading mitochondrial lipids during maturation of the reticulocyte to the erythrocyte; and the second, mouse glutathione peroxidase (GSHPX), an important seleno-enzyme responsible for protection against peroxide-damage. Characterization of the GSHPX gene revealed that the seleno-cysteine residue in the active site of the enzyme is encoded by UGA, which usually functions as a translation-termination codon. This novel finding has important implications regarding the role of mRNA sequence context effects in codon recognition. In contrast with the beta-globin locus, very little is known about the mechanisms responsible for the erythroid-specific expression of the alpha-globin genes. By a combination of functional transfection assays and studies of the interactions of nuclear sequence-specific DNA-binding proteins with promoter sequences in vitro, we have recently defined two regions upstream of the mouse alpha-globin gene involved in its erythroid-specific expression: one contains a sequence motif (GATAAG) that binds to a species-conserved and erythroid-specific factor both in vitro and in vivo. Interestingly, GATAAG motifs binding the same factor are found also in the mouse and chicken adult beta-globin gene promoters, the erythroid-specific promoter of the haem pathway enzyme, porphobilinogen (PBG) deaminase and the chicken beta-globin 3' enhancer. We are now commencing purification of this erythroid-specific GATAAG-binding factor, investigating in more detail how it functions in relation to other globin gene control regions and determining whether GATAAG-like regions have a functional role in the erythroid-specific expression of other genes. We have begun to investigate the regulation of the GSHPX and red cell LOX genes. The presence of tissue-specific 3' DNAse I-hypersensitive sites (DHSS) suggests that different 3' flanking regions of the GSHPX gene may be important in its regulation in the various cell types in which it is highly expressed, i.e. erythroid cells, liver and kidney.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Peripheral progesterone concentrations in the luteal-phase ewe: effects of a beta-adrenergic receptor antagonist and two beta 2-adrenergic agonists.

Peripheral blood samples were collected at 10-min intervals from three conscious sheep in which ovulation had been induced 6-10 days previously using exogenous hormones. Saline was infused into a jugular vein for about 1 h, followed by the experimental drug for 1-2 h and followed by saline again for a further 2 h. The experiments were repeated following induced luteolysis and ovulation. The infusion of a beta-adrenergic antagonist (propranolol) into three conscious luteal-phase ewes decreased (P less than 0.05) the peripheral progesterone concentration in each animal. Infusions of beta 2-adrenergic agonists (ritodrine and salbutamol) increased (P less than 0.05) the progesterone concentration in four out of eight experiments. The beta-adrenergic antagonist decreased the heart rate and the beta 2-adrenergic agonist increased it; the arterial blood pressure and respiratory rate were unaffected. The decrease in the progesterone concentration in response to the beta-adrenergic antagonist suggests that the normal ovarian secretion of progesterone is partly the result of sympathetic stimulation, and that the sympathetic innervation of the ovary may have a physiological role in modulating progesterone secretion.

Albuterol↗

Chemotherapy for malignant gliomas.

There continues to be an extensive effort to develop chemotherapeutic approaches to the treatment of malignant gliomas of the brain. In the past 5 years there have been literally hundreds of trials of new agents, combinations of old and new agents, and even new routes and approaches to the delivery of chemotherapy. In this review, the literature has been studied and the individual reports analyzed to evaluate the impact of the new findings on clinical management of the patient with malignant glioma of the brain. The major areas of progress include the addition of new drugs with varying modes of action, the use of combinations of drugs in a synergistic fashion, and the development of new routes of drug delivery. None of the advances has brought about the revolution in clinical care that is so eagerly sought, but clearly the amount of new knowledge gained by these studies helps in understanding how to use chemotherapy more effectively. Furthermore, the remarkable degree of interest and involvement in the use of chemotherapy promises that an even greater number of patients with malignant gliomas will be considered for vigorous and enthusiastic clinical management programs even if chemotherapy itself is not the key modality in the treatment of a specific patient.

Adrenal Cortex Hormones↗